Research into the biochemical and behavioral effects of two classes of drugs of abuse, stimulants and hallucinogens, has concentrated on the role of the catecholamines and indoleamines, respectively, as possible neurotransmitters mediating the behavioral effects of these drugs. However, recent work has suggested that these drugs all share dopaminergic agonistic actions. Furthermore, previous research on the dopaminergic effects of cocaine, amphetamine, LSD, and mescaline has concentrated on the nigro-striatal dopamine system with less emphasis on the meso-limbic system. In the first set of experiments, we will examine the facilitative effects of hallucinogens on shuttlebox avoidance behavior. These effects are likely to be mediated by the dopaminergic properties of hallucinogens. These studies will increase or decrease the function of the dopamine systems by acute pretreatment with dopamine blockers, lesions of the presynaptic components of the dopamine systems, withdrawal from chronic treatment with dopamine blockers, or lesion-induced denervation supersensitivity. Effects of these manipulations on the hallucinogen-induced behavioral effects will be assessed. A second series of experiments will examine behavioral changes following long-term stimulant treatment. These experiments will study the role of conditioning in the augmentation of the behavioral effects following chronic amphetamine and cocaine administration. Further studies will investigate the pharmacology and pre- and post-synaptic biochemistry of conditioning. Related studies will examine biochemical changes that occur in dopamine systems following chronic treatment with stimulants and which result in behavioral potentiation. We will compare and contrast the changes due to conditioning with those due to non-conditioned chronic drug effects. The following will be studied: 1) dopaminergic properties of the hallucinogens related to behavior; 2) differential effects of the hallucinogens on the meso-limbic and nigro-striatal dopamine systems; 3) role of conditioning in the behavioral and biochemical effects of long term administration of hallucinogens and stimulants on dopamine; and 4) differences both behaviorally and biochemically between acute and chronic effects of these drugs.